title: Inflammation provoked by Mycoplasma pneumoniae extract: implications for combination treatment with clarithromycin and dexamethasone.
abstract: Recently, combination treatment with a macrolide and a steroid for Mycoplasma pneumoniae (Mp) pneumonia has been reported to be effective. Thus, the effect of this combination on a mouse model of lung inflammation associated with Mp extract (the LIMEX mouse) was studied. Interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were induced in Mp extract-treated RAW264.7 cells, and this induction was inhibited by dexamethasone, parthenolide, SB203580 or LY294002. This suggested that Mp extract activates nuclear factor κB-, p38- and PI-3K-linked pro-inflammatory signals. The LIMEX mice were then either treated with or without clarithromycin and/or dexamethasone. Clarithromycin administration enhanced the production of IL-6, TNF-α, macrophage inflammatory protein-1α, monocyte chemotactic protein-1 and RANTES, while their production was perfectly suppressed by the combination of clarithromycin and dexamethasone. IL-17, IL-23, keratinocyte-derived chemokine (KC) and interferon-γ levels were not affected by clarithromycin treatment, but they were significantly suppressed by the combination of dexamethasone and clarithromycin. Collectively, some components of Mp extract provoked an inflammatory reaction in the RAW 264.7 cell line and LIMEX mice. Whereas the lung reaction in LIMEX mice was further exacerbated by clarithromycin treatment, it was resolved by the combinational treatment with clarithromycin and dexamethasone.
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Hirao
authors.forename: Hiroo
authors.initials: H
authors.lastname: Wada
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Nakagaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saraya
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurai
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Mikura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yasutake
authors.forename: Manabu
authors.initials: M
authors.lastname: Higaki
authors.forename: Takuma
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Ishii
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
authors.forename: Toshi
authors.initials: T
authors.lastname: Aakashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kamiya
authors.forename: Hajime
authors.initials: H
authors.lastname: Goto
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002460:Cell Line; D017291:Clarithromycin / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D007249:Inflammation / Q000139:chemically induced*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009177:Mycoplasma pneumoniae / Q000187:drug effects / Q000472:pathogenicity*; D011019:Pneumonia, Mycoplasma / Q000188:drug therapy / Q000473:pathology*
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003907:Dexamethasone; D017291:Clarithromycin